Department of Clinical and Experimental Medicine, Ingrid Asp Psoriasis Research Center, Linköping University, Linköping, Sweden.
Department of Dermatology, University of Michigan, Ann Arbor, MI, U.S.A.
Br J Dermatol. 2016 Dec;175(6):1263-1273. doi: 10.1111/bjd.14718. Epub 2016 Oct 5.
Vascular modifications occur early in the development of psoriasis, and angiogenesis is one of the key features in the pathogenesis of the disease.
To identify the role of the S100 protein psoriasin in psoriasis-associated angiogenesis.
The role of psoriasin in mediating angiogenesis was investigated by silencing psoriasin with small interfering RNA (siRNA) and measuring psoriasis-associated angiogenic factors in human epidermal keratinocytes. The secretion of psoriasin and the effect of psoriasin on general regulators of angiogenesis in keratinocytes, and on endothelial cell migration, proliferation, tube formation and production of angiogenic mediators, was evaluated.
Reactive oxygen species (ROS) and hypoxia induced the expression of psoriasin. Downregulation of psoriasin in keratinocytes using siRNA altered the ROS-induced expression of the psoriasis-associated angiogenic factors vascular endothelial growth factor (VEGF), heparin-binding epidermal growth factor-like growth factor, matrix metalloproteinase 1 and thrombospondin 1. Overexpression of psoriasin altered several regulators of angiogenesis and led to the secretion of psoriasin. Treatment with extracellular psoriasin induced proliferation, migration and tube formation in dermal-derived endothelial cells to a similar extent as VEGF and interleukin-17, and induced the expression and release of proangiogenic mediators. These effects were suggested to be mediated by the PI3K and nuclear factor kappa B pathways.
These findings suggest that psoriasin expression is promoted by oxidative stress in keratinocytes and amplifies the ROS-induced expression of angiogenic factors relevant to psoriasis. Moreover, extracellularly secreted psoriasin may act on dermal endothelial cells to contribute to key features angiogenesis.
血管改变发生在银屑病发展的早期，而血管生成是疾病发病机制的关键特征之一。
确定 S100 蛋白银屑病相关素在银屑病相关血管生成中的作用。
通过用小干扰 RNA（siRNA）沉默银屑病相关素来研究银屑病相关素在介导血管生成中的作用，并测量人表皮角质形成细胞中与银屑病相关的血管生成因子。评估银屑病相关素的分泌及其对角质形成细胞中血管生成一般调节剂的作用，以及对内皮细胞迁移、增殖、管形成和血管生成介质产生的影响。
活性氧（ROS）和缺氧诱导银屑病相关素的表达。用 siRNA 下调角质形成细胞中的银屑病相关素改变了 ROS 诱导的与银屑病相关的血管生成因子血管内皮生长因子（VEGF）、肝素结合表皮生长因子样生长因子、基质金属蛋白酶 1 和血栓素 1 的表达。银屑病相关素的过表达改变了几种血管生成调节剂，并导致银屑病相关素的分泌。细胞外银屑病相关素处理诱导真皮来源的内皮细胞增殖、迁移和管形成，其程度与 VEGF 和白细胞介素 17 相似，并诱导促血管生成介质的表达和释放。这些作用被认为是通过 PI3K 和核因子 kappa B 途径介导的。
这些发现表明，角质形成细胞中的氧化应激促进了银屑病相关素的表达，并放大了 ROS 诱导的与银屑病相关的血管生成因子的表达。此外，细胞外分泌的银屑病相关素可能作用于真皮内皮细胞，有助于关键特征血管生成。
